Nucleoside 5′-Phosphorothioate Derivatives as Oxidative Stress Protectants in PC12 Cells

Abstract

Iron-induced oxidative damage of mitochondria contributes to cellular death seen in neurodegenerative diseases, therefore, there is a demand for nontoxic, biocompatible, and effective Fe-ion chelators. We evaluated the chelation of Fe(II) by phosphate derivatives using ferrozine as an indicator. We studied the effect of phosphate derivatives on inhibiting Fe(II)-induced oxidative stress in PC12 cells, and metabolic stability in PC12 cells was evaluated. Nucleotides containing phosphorothioate moieties inhibited ROS formation better than natural nucleotides and were more metabolically stable in PC12 cells. Finally, we elucidated that these nucleotides activate the MAP-kinase pathway that contributes to protection of PC12 cells under oxidative stress.

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Keywords:

• Antioxidant
• reactive oxygen species
• phosphorothioate derivative
• oxidative stress
• ferrous ion
• metabolic stability

Acknowledgments

The authors thank Mr. Alon Sayer for his generous contribution of phosphorothioate derivatives.